Clinical Infections by Herpesviruses in Patients Treated with Valproic Acid: A Nested Case-Control Study in the Spanish Primary Care Database, BIFAP.

The objective of this study is to evaluate the risk of clinical infections by herpesviruses in patients exposed to valproic acid (VPA). We performed a case-control study nested in a primary cohort selected from the Spanish primary care population-based research database BIFAP (Base de datos para la Investigacion Farmacoepidemiologica en Atencion Primaria) over the period 2001-2015. The events of interest were those diseases caused by any herpesviruses known to infect humans. For each case, up to 10 controls per case matched by age, gender, and calendar date were randomly selected. A conditional logistic regression was used to compute adjusted odds ratios (OR) and their 95% confidence intervals (95% CI). Current use of VPA was associated with a trend towards a reduced risk of clinical infections by herpesviruses as compared with non-users (OR 0.84; CI 95% 0.7-1.0; p = 0.057). Among current users, a trend to a decreased risk with treatment durations longer than 90 days was also observed. The results show a trend to a reduced risk of clinical infection by herpesviruses in patients exposed to VPA. These results are consistent with those in vitro studies showing that, in cultured cells, VPA can inhibit the production of the infectious progeny of herpesviruses. This study also shows the efficient use of electronic healthcare records for clinical exploratory research studies.